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Neurons. A nerve cell capable of generating and transmitting electrical signals Vary in structure and properties Use the same basic mechanisms to send signals Generate action potentials or passive potential
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Neurons • A nerve cell capable of generating and transmitting electrical signals • Vary in structure and properties • Use the same basic mechanisms to send signals • Generate action potentials or passive potential • Communicate with other neurons or cells via synaptic connections (electrical or chemical)
Neural Zones • Four functional zones • Signal reception: dendrites and the cell body (soma) - Incoming signal is received and converted to a change in membrane potential • Signal integration: axon hillock - Strong signal action potential (AP) • Signal conduction: axon; some wrapped in myelin sheath - AP travels down axon • Signal transmission: axon terminals - Neurotransmitter is released
Electrical Signals in Neurons • Neurons have a resting membrane potential (like all cells) • Neurons are excitable; can rapidly change their membrane potential • Changes in membrane potential act as electrical signals
Measuring the voltage • Use microelectrodes to measure the voltage between outside and inside • Conducting fluid such as KCL is used • Reference electrode is placed in the bathing medium • Potentiometer will measure the potential ie • resting potential
Membrane Potential • Three factors contribute to the membrane potential • The distribution of ions across the plasma membrane • The relative permeability of the membrane to these ions • The charges of the ions ►Nernst equation can be used to measure the potential of a cell ie the voltage difference between the inside and the outside of the cell.
Membrane Potential EK+ = (1.9872*295)/(1*23062) ln (4/139) = - 88 mV at 22oC ENa+ = (1.9872*295)/(1*23062) ln (145/12) = 62 mV at 22oC ECl- = (1.9872*295)/(-1*23062) ln (116/4) = - 84 mV at 22oC
Resting potential Origin of the resting potential in a typical vertebrate neuron. • A- - negatively charged proteins • Resting neuron: 10 times more open K+ channels than Na+ or Cl- channels • Outside of cell is more positive relative to the inside of the cell • K+ isdominant because its permeability is greatest (PK). This is due to leak channels • So the resting potential is closest to the Nernst potential for K+ • Also have leakage of Na+ (PNa) and Cl- (PCl)
Resting potential Actual measurements of membrane potential • Measured in giant axon of squid • Found resting potential of -65 to -70 mV • Increased external K+ to determine new membrane potential • Found a slope of – 58 mV ► means that for every ten fold increase in external K+ the potential will increase by 58 mV at room temperature • So other ions are influencing the resting potential!! • Permeability of Na+ and Cl- ions and the presence of proteins. • Use Goldman equation to calculate the resting potential
Membrane Potential • Nernst equation predicts membrane potential for a single ion • Goldman equation for the membrane potential (Em): predicts the membrane potential using multiple ions Chloride ion has a charge opposite to the two cations, a correction is needed to prevent the cations and anion from canceling each other. Thus, the statement of relative chloride ion concentrations is inverted— inside over outside In the giant squid: PK+ : PNa+ : PCl- = 1 : 0.04 : 0.45
Membrane Potential • Effects of changing the ion permeability The resting membrane potential is -53 mV; ENa, EK, and ECl are the potentials calculated from the Nernst equation if the membrane contains only open channels for Na+ or K+ or Cl-, respectively.
Electrical signals • Changes in Channel permeability create Electrical signals! • Mechanically gated ion channels • Sensory neurons. Open in response to pressure or stretch • Chemically gated ion channels • Respond to ligands • Voltage gated Na+ channels • Respond to changes in membrane potential • Voltage gated K+ channels or CA2+ channels
Graded Potential vs. Action Potential Two types of electrical signals
Action potentials Active conduction • Passive conduction of signal is limited by properties of the nerve and signal is reduced over distance • Active conduction ie action potentials (AP) • - Signal travels along nerve with no loss of amplitude
Action Potentials (AP) • Occurs only when the membrane potential at the axon hillock reaches threshold • Three phases • Depolarization • Repolarization • Hyperpolarization • Absolute refractory period – incapable of generating a new AP • Relative refractory period – more difficult to generate a new AP
Voltage-Gated Channels • Change shape due to changes in membrane potential • Positive feedback, e.g., influx of Na+ local depolarization number of open Na+ channels • Na+ channels open first (depolarization) • K+ channels open more sloooooowly (repolarization) • Na+ channels close • K+ channels close slooooowly (relative refractory period)
Channels of an Action potentials Voltage gated Na+ channels: 3 states: closed, open, inactive Closed to open: • Depolarization is necessary to open the channel • Acts to activate itself in a regenerative cycle • More Na+ influx depolarizes the membrane which opens more channels which depolarizes the membrane more. • Open to Inactive: • Depolarization is also necessary to inactive the channel • Once the channel is open it will then also switch to the inactive state and can not be opened again • Inactive to closed: • The channel will not switch back to the closed state until the membrane has repolarized (i.e. gone back towards the original resting membrane potential • Once in the closed state it can then be reopened
Na+ Channels Have Two Gates • Activation gate – voltage dependent • Inactivation gate – time-dependent
Channels of an Action potentials Voltage gated K+ channels (delayed rectifying K+ channel): 2 states: closed and open Closed to open: • Strong depolarization is necessary to open the channel • Hyperpolarizes the cell • Brings membrane back towards Nernst potential for K+ • Open to Closed: • Will close when the membrane becomes hyperpolarized • Works to shut itself down
Action Potentials Travel Loooong Distances • “All-or-none” – occurs or does not occur; identical without degradation • Self propagating - an AP triggers the next AP in adjacent areas of the axonal membrane • Electronic current spread in between ion channels • Cycle: Ion entry electronic current spread triggering AP
Components of an Action potentials • Threshold • Most neurons have a threshold at -50 mV (i.e. 10 to 15 mV depolarization) • Action potential is an all or none event. If a nerve is at rest the amplitude • on one action potential will be the same all along the nerve independent of the • stimulus strength • Threshold reflects the need to trigger the opening of the voltage-gated • sodium channel (need a depolarization of about 10 to 15 mV to open) • Rising phase • Sodium channels open • Na+ ions flow into cell • Depolarizes the cell • More and more sodium channels open = a regenerative response regenerative opening of sodium channels drives the membrane potential towards a peak of the Nernst equilibrium potential for Na+
Components of an Action potentials • Peak • During an action potential the membrane potential goes towards the • Nernst equilibrium potential for Na+ • In terms of Goldman-Katz equation now permeability to Na+ is dominant • (K+ and Cl- minor components) therefore membrane potential goes towards • ENa • Usually falls short of ENa, less driving force on Na+ and the channels begin • to inactivate rapidly after activation
Components of an Action potentials • Fall • Membrane potential falls back towards rest- Why doesn't the action potential stay around ENa?Two reasons: i) Na+ channels move into an inactive stateii) delayed K+ channels open • Inactivating Na+ channels- Na+ channels go to an inactivated state after 1-2 msec after first opening - inactivated = can NOT be reopened- Membrane potential now determined mostly by K+ (same as for resting potential) and membrane starts to repolarize • Delayed K+ channels open (delayed rectifier; voltage-gated like Na+ channel)- open after about 1-2 msec of threshold depolarization- now K+ flows out of the cell and speeds the repolarization process- cause the hyperpolarizationafter the action potential - open K+ channels make the K+ permeability higher than at rest - membrane more negative on inside - hyperpolarization of membrane causes K+ channels to close - Membrane settles back to rest
Components of an Action potentials • Repolarization • Voltage-gated Na+ channels and voltage-gated K+ channels now closed • Membrane goes back to the resting state- i.e. the leak channels are the only channels open and again set the membrane potential
Unidirectional Signals • Stimulus starts at the axon hillock and travels towards the axon terminal • Up-stream Na+ channels (just recently produced an AP) are in the absolute refractory period • The absolute refractory period prevents backward transmission and summation of APs • Relatively refractory period also contributes by requiring a very strong stimulus to cause an AP
Refractory period (RP) Absolute RP • Na+ channels are inactive and CAN NOT be opened no matter how much • the membrane is depolarized at this time • another action potential can not be generated Relative RP • Membrane repolarizes ---- • goes to more negative potentials • Triggers the Na+ channels to move • from an inactive state to a close state • Hyperpolarization by the opening of the • K+ channels • Once Na+ channel is in the closed state • it can be opened again with depolarization • during relative RP, more and more • Na+ channels available to be opened and • therefore increase the chances of firing • an action potential
Frequency of AP How does a nerve communicate the strength of a stimulus? • Information is given by the frequency of the AP along the nerve • Stimulus strength triggers different frequency of AP • For example: light touch – infrequent AP; • rough touch – more frequent AP • Refractory period limits the frequency of AP • During the relative RP an AP can be generated • but has to be at supra threshold because it has to • overcome the hyperpolarization • Will be at decreased amplitude because • fewer Na+ channels are available to open
Direction of AP Unidirectional conduction of an action potential due to transient inactivation of voltage-gated Na+ channels
Action Potentials Travel Loooong Distances • Triggered by the net graded potential at the axon hillock(trigger zone) • Do not degrade • Travel looong distances • All-or-none • Must reach threshold potential to fire
Signals in the Dendrites and Cell Body • Incoming signal, e.g., neurotransmitter • Membrane-bound receptors transduce the chemical signal to an electrical signal by changing the membrane potential (graded potential)
Graded Potentials • Vary in magnitude depending on the strength of the stimulus • e.g., more neurotransmitter more ion channels will open
Graded Potentials • Ions move down an electrochemical gradient • Net movement stops when the equilibrium potential is reached • Can depolarize (Na+ and Ca2+ channels) or hyperpolarize (K+ and Cl- channels) the cell
Graded Potentials Travel Short Distances • Conduction with decrement – strength with distance from opened ion channel • Due to • Leakage of charged ions across the membrane • Electrical resistance of the cytoplasm • Electrical properties of the membrane • Electrotonic current spread – positive charge spreads through the cytoplasm causing depolarization of the membrane • Can be excitatory or inhibitory
Integration of Graded Signals • Many graded potentials can be generated simultaneously • Many receptor sites • Many kinds of receptors • Temporal summation – graded potentials that occur at slightly different times can influence the net change • Spatial summation – graded potentials from different sites can influence the net change